Amides, C8-18(even-numbered) and C18(unsatd.), N-(2-hydroxypropyl)

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

From February 20, 1996 to April 4, 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

KL2 due to RA

Justification for type of information:

Refer to the section 13 for details on the category justification.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate, Kent, UK
- Age at study initiation: 5-8 wk
- Weight at study initiation: Males - 152 - 182 g, females - 140-156 g
- Fasting period before study: Overnight
- Housing: Groups of up to five by sex in solid-floor polypropylene cages
- Diet: Rat and mouse expanded diet no. 1, ad libitum
- Water: Drinking water, ad libitum
- Acclimation period: Atleast 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 44-65
- Air changes (per h): 15
- Photoperiod (h dark/h light): 12/12

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

2000 mg/kg in both range-finding and main study

No. of animals per sex per dose:

One in range-finding study and five in main study

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of clinical observation: 0.5, 1, 2 and 4 h after dosing and subsequently once daily for 14 d
- Frequency of weighing: On Days 0, 7 and 14
- Necropsy of survivors performed: Yes
- Examinations performed: Clinical signs, body weight and gross pathological examination

Statistics:

None.

Preliminary study:

No deaths or clinical signs of toxicity.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality.

Clinical signs:

other: other: No signs of systemic toxicity.

Gross pathology:

No abnormalities noted at necropsy.

None.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the LD50 was determined to be >2000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute oral toxicity of the read across substance, C8-18 and C18-unsatd. MEA, to Sprague Dawley rats according to OECD Guideline 401 and EU Method B.1, in compliance with GLP. Following a range-finding study, a group of 10 fasted rats (five males and five females) were given a single oral dose of the test substance as a solution in arachis oil BP at a dose level of 2000 mg/kg bw. The animals were observed for 14 d after dosing and were then killed and subjected to gross pathological examination. There was no mortality in the study and no signs of systemic toxicity were noted. All animals showed an expected gain in body weight apart from one female which showed reduced body weight gain during the second week. No abnormalities were noted at necropsy. Under the study conditions, the LD50 was determined to be >2000 mg/kg bw (Hempstock, 1996). Based on the results of the read across study, a similar LD50 value is expected for the test substance.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Study period:

From November 11, 1992 to March 25, 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

KL2 due to RA

Justification for type of information:

Refer to the section 13 for details on the category justification.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

humidity; not but considered to have affected the outcome or the objectives of the study

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

yes

Remarks:

humidity; not but considered to have affected the outcome or the objectives of the study

GLP compliance:

yes

Test type:

other: acute oral toxicity

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Supplier: Iffa-Credo, B.P. 0109 (69592 L’Arbresle Cedex - France)
Acclimatisation: 5 days minimum
Age at initiation of treatment: adult 5 to 7 weeks old
Body weight range at initiation of treatment: males : 130 to 230g and females: 120 to 180g
Temperature : 19 to 25°C (target range)
Relative humidity : 30 to 70 % R.H. (target range)
Air changes: minimum 8 air changes per hour
Lighting cycle: 12 hours light (artificial)/12 hours dark
Diet: pelleted complete diet, ad libitum and water: filtered (0.2 µm) drinking water, ad libitum

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Method: single oral administration by gastric gavage (using a metal canulla)
Volume administered: 2.18 mg/kg bw

Doses:

2006 mg/kg bw (based on a preliminary study)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Duration of observation period following administration: 14 days

Preliminary study:

Determination of the dose for the limit test: 2000 mg/kg

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 006 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality was observed.

Clinical signs:

other: other: There were no changes in behaviour or clinicai signs in any of the treated animals during the observation period.

Gross pathology:

There were no macroscopic findings that could be associated with treatment.

None.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the oral LD50 was determined to be >2006 mg/kg bw.

Executive summary:

A study was conducted to determine the acute oral toxicity of the read across substance, isoC18 MIPA (100% active), according to OECD Guideline 401 and EU Method C.1, in compliance with GLP. Groups of 5 male and 5 female Wistar rats received a single dose of 2006 mg/kg bw by oral gavage (2.18 mL/kg bw). This administration was followed by a 14 d observation period. Examinations for mortality and abnormal clinical signs were performed 15 min after administration, then at 1, 2 and 4 h, and thereafter daily for the 14 d study period. All the animals were weighed the day before treatment, immediately before administration of the test substance (Day 1), then on Days 8 and 15. A necropsy was performed for all the animals after the final in vivo observation on Day 15. No mortality was observed. There were no changes in behaviour or clinicai signs in any of the treated animals throughout the study. Body weight changes were within the expected range. There were no macroscopic findings that could be associated with treatment. Under the study conditions, the oral LD50 was determined to be >2006 mg/kg bw (Lheritier, 1993). Based on the results of the read across study, a similar LD50 value is expected for the test substance.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Adequate

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Clinical signs:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Justification for type of information:

Refer to the section 13 for details on the category justification.

Qualifier:

according to guideline

Guideline:

other: A modification of the techniques described in Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, compiled by the staff of the Division of Pharmacology, Food and Drug Administration.

Deviations:

not specified

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Weight at study initiation: 1.9-2.7 kg

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Prior to dosing, the trunk of each animal was clipped free of hair. Three of the animals (two male, one female) were further prepared by introducing epidermal abrasions over the clipped skin surface to enhance penetrability of the test substance through the stratum corneum. After test substance application the trunk of each animal was encased in a sleeve of plasticized material for 24 h. Following the 24 h exposure period the sleeve was removed and the skin sites gently cleansed.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Details on study design:

All animals were observed daily thereafter for 14 d for mortality, skin response and general behavior.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortalities observed.

Clinical signs:

other: other: All animals appeared normal through Day 14.

None.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the acute dermal LD50 was determined to be >2000 mg/kg bw.

Executive summary:

A limit test was conducted to determine the acute dermal toxicity of the read across substance, C8-18 and C18-unsatd. MEA, to albino rabbits. Three male and three female rabbits were administered a single dose of the read across substance at a level of 2000 mg/kg bw. Prior to dosing, the trunk of each animal was clipped free of hair. Three of the animals (two males and one female) were further prepared by introducing epidermal abrasions over the clipped skin surface to enhance penetrability of the read across substance through the stratum corneum. After test substance application, the trunk of each animal was encased in a sleeve of plasticized material for 24 h. Following the exposure period, the sleeve was removed and the skin sites gently cleansed. All animals were observed daily thereafter for 14 d for mortality, skin response and general behavior. All animals survived and appeared normal through to Day 14. Two females that had abraded skin lost weight over the 14 d post-exposure period. All remaining rabbits gained weight. Under the study conditions, the acute dermal LD50 was determined to be >2000 mg/kg bw (Palanker, 1976). Based on the results of the read across study, a similar LD50 value is expected for the test substance.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

From March 30, 1999 to April 13, 1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

KL2 due to RA

Justification for type of information:

Refer to the section 13 for details on the category justification.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

other: HanIbm: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Source: RCC Ltd Biotechnology & Animal Breeding Division CH-4414 Füllinsdorf / Switzerland
Age when treated: 9 weeks for the males and 12 weeks for the females
Temperature: 22 +/- 3°C and relative humidity: 40-70%
Light period: 12 hour light/dark cycle
Diet: pelleted Standard Kliba 3433, ad libitum and water: community tap water, ad libitum

Type of coverage:

semiocclusive

Vehicle:

polyethylene glycol

Details on dermal exposure:

The test substance was placed into a glass beaker on a tared Mettler balance and the vehicle (polyethylene glycol PEG 300) was added. A weight by volume dilution was prepared using a magnetic stirrer as homogenizer. Homogeneity of the test substance in the vehicle was maintained during treatment. The preparation was made shortly before dosing.
Approximately 24 hours before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10% of the total body surface. Only those animals without injury or irritation on the skin were used in the test. On test day 1, the test substance was applied at a dose of 2000 mg/kg bw evenly on the intact skin with a syringe and covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage. Application volume/kg bw: 4.0 mL. Twenty-four hours after the application the dressing was removed and the skin was flushed with lukewarm tap water and dried with disposable paper towels. Thereafter, the reaction sites were assessed.

Duration of exposure:

24h

Doses:

2000 mg/kg bw (at a concentration of 0.5 g/mL in vehivle and administered at a volume of 4 mL/kg)

No. of animals per sex per dose:

5

Control animals:

no

Statistics:

No statistical analysis was used as no deaths occurred.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No deaths occurred during the study.

Clinical signs:

other: other: No clinical signs were observed during the observation period.

Gross pathology:

No macroscopic findings were observed at necropsy.

None.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the dermal LD50 was determined to be >2000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute dermal toxicity of the read across substance, isoC18 MIPA (100% active), according to OECD Guideline 402 and EU Method B.3, in compliance with GLP. Groups of 5 male and 5 female HanIbm: WIST (SPF) rats were exposed to the test substance (in polyethylene glycol) at a concentration of 2000 mg/kg bw via a semi-occlusive dermal application (4 mL/kg bw) for 24 h. This application was followed by a 14 d observation period. The animals were examined for clinical signs four times during Day 1 and once daily during Days 2-15. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on Day 1 prior to administration and on Days 8 and 15. All animals were necropsied and examined macroscopically. No deaths occurred during the study. No clinical signs were observed throughout the observation period. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were noted at necropsy. Under the study conditions, the dermal LD50 was determined to be >2000 mg/kg bw (Ullmann, 1999). Based on the results of the read across study, a similar LD50 value is expected for the test substance.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Adequate

Additional information

Oral

A study was conducted to determine the acute oral toxicity of the read across substance, C8-18 and C18-unsatd. MEA, to Sprague Dawley rats according to OECD Guideline 401 and EU Method B.1, in compliance with GLP. Following a range-finding study, a group of 10 fasted rats (five males and five females) were given a single oral dose of the test substance as a solution in arachis oil BP at a dose level of 2000 mg/kg bw. The animals were observed for 14 d after dosing and were then killed and subjected to gross pathological examination. There was no mortality in the study and no signs of systemic toxicity were noted. All animals showed an expected gain in body weight apart from one female which showed reduced body weight gain during the second week. No abnormalities were noted at necropsy. Under the study conditions, the LD50 was determined to be >2000 mg/kg bw (Hempstock, 1996).

A study was conducted to determine the acute oral toxicity of the read across substance, isoC18 MIPA (100% active), according to OECD Guideline 401 and EU Method C.1, in compliance with GLP. Groups of 5 male and 5 female Wistar rats received a single dose of 2006 mg/kg bw by oral gavage (2.18 mL/kg bw). This administration was followed by a 14 d observation period. Examinations for mortality and abnormal clinical signs were performed 15 min after administration, then at 1, 2 and 4 h, and thereafter daily for the 14 d study period. All the animals were weighed the day before treatment, immediately before administration of the test substance (Day 1), then on Days 8 and 15. A necropsy was performed for all the animals after the final in vivo observation on Day 15. No mortality was observed. There were no changes in behaviour or clinicai signs in any of the treated animals throughout the study. Body weight changes were within the expected range. There were no macroscopic findings that could be associated with treatment. Under the study conditions, the oral LD50 was determined to be >2006 mg/kg bw (Lheritier, 1993).

Dermal

A limit test was conducted to determine the acute dermal toxicity of the read across substance, C8-18 and C18-unsatd. MEA, to albino rabbits. Three male and three female rabbits were administered a single dose of the read across substance at a level of 2000 mg/kg bw. Prior to dosing, the trunk of each animal was clipped free of hair. Three of the animals (two males and one female) were further prepared by introducing epidermal abrasions over the clipped skin surface to enhance penetrability of the read across substance through the stratum corneum. After test substance application, the trunk of each animal was encased in a sleeve of plasticized material for 24 h. Following the exposure period, the sleeve was removed and the skin sites gently cleansed. All animals were observed daily thereafter for 14 d for mortality, skin response and general behavior. All animals survived and appeared normal through to Day 14. Two females that had abraded skin lost weight over the 14 d post-exposure period. All remaining rabbits gained weight. Under the study conditions, the acute dermal LD50 was determined to be >2000 mg/kg bw (Palanker, 1976).

A study was conducted to determine the acute dermal toxicity of the read across substance, isoC18 MIPA (100% active), according to OECD Guideline 402 and EU Method B.3, in compliance with GLP. Groups of 5 male and 5 female HanIbm: WIST (SPF) rats were exposed to the test substance (in polyethylene glycol) at a concentration of 2000 mg/kg bw via a semi-occlusive dermal application (4 mL/kg bw) for 24 h. This application was followed by a 14 d observation period. The animals were examined for clinical signs four times during Day 1 and once daily during Days 2-15. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on Day 1 prior to administration and on Days 8 and 15. All animals were necropsied and examined macroscopically. No deaths occurred during the study. No clinical signs were observed throughout the observation period. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were noted at necropsy. Under the study conditions, the dermal LD50 was determined to be >2000 mg/kg bw (Ullmann, 1999).

Justification for classification or non-classification

Based on acute oral and dermal LD50 values >2000 mg/kg bw, the substance does not require classification for acute endpoints according to CLP (EC 1272/2008) criteria.